Balloon Catheter

ABSTRACT

A catheter is provided comprising a flexible heat transfer element provided on an outer surface of the catheter, a conduit arranged to supply an inflation fluid for inflating the flexible heat transfer element so as to form an inflated balloon, a guide wire lumen for receiving a guide wire, and an elongate cooling element arranged to cool said inflation fluid for inflating the balloon. Said cooling element and said guide wire lumen are arranged inside the flexible heat transfer element such that, when inflated the cooling element is substantially central within the balloon and said guide wire lumen is parallel to and radially offset from the cooling element.

CROSS-REFERENCE TO RELATED APPLICATIONS

The present application is a continuation application of and claimspriority to U.S. patent application Ser. No. 16/300,602, filed Nov. 12,2018, and issuing as U.S. Pat. No. 10,940,036 on Mar. 9, 2021, which isa U.S. national stage entry under 35 U.S.C. § 371 of Patent CooperationTreaty Application No. PCT/EP2017/061090, filed May 9, 2017, whichclaims priority to U.S. Provisional Patent Application No. 62/335,885,filed May 13, 2016. All foregoing applications are incorporated hereinby reference in their entireties.

FIELD

The present invention relates to balloon catheters for the invasivetreatment of a body. The catheter comprises an elongate cooling elementarranged centrally within a balloon to provide even cooling across thesurface of the balloon.

BACKGROUND

From the late 1970's, catheters for cryotherapy have been used in thecardiovascular system starting from, for example, 1977 when it was usedto surgically treat cardiac arrhythmias. Over the ensuing years itbecame widely recognised that cryotherapy was particularly advantageousfor working in the heart. Its safety and efficacy was unsurpassed assurgeons were able to ablate delicate cardiac structures such as the A-Vnode, pulmonary veins and delicate peri-nodal atrial tissue withoutconcern for thrombosis, perforation or other adverse events.

A catheter for the treatment of plaque stabilisation by cryotherapy isdescribed in WO 2015/067414 (referred to hereinafter as WO'414). Aballoon is inflated around a catheter shaft and subsequently cooled. Aco-axially arranged cooling element is used to achieve this, wherein aliquid coolant is conveyed from an inner supply lumen into a largerconduit. When exiting the supply lumen the coolant undergoes a phasechange due to the pressure drop which occurs, causing it to evaporateand reduce in temperature. The cold gas is then removed using a returnlumen which surrounds the supply lumen in a co-axial manner.

A number of advantages are provided by the above co-axial design, asdiscussed in WO'414. For example, a single layered balloon may be usedsince there is little risk of a gas coolant leaking from the catheter.Furthermore cooling occurs, via the phase change, in the location whereit is required without the need for insulating layers to be provided.Further still, the cooling element and its supporting lumen may maintaina small cross sectional area, making it suitable for applications insmall diameter arteries, for example for the treatment of coronaryvascular diseases. There remains a need however to improve known designsof catheters for cryotherapy.

SUMMARY OF THE INVENTION

According to an aspect of the invention, there is provided a cathetercomprising: a flexible heat transfer element provided on an outersurface of the catheter; a conduit arranged to supply an inflation fluidfor inflating the flexible heat transfer element so as to form aninflated balloon; a guide wire lumen for receiving a guide wire; and anelongate cooling element arranged to cool said inflation fluid forinflating the balloon; wherein said cooling element and said guide wirelumen are arranged inside the flexible heat transfer element such that,when inflated the cooling element is substantially central within theballoon and said guide wire lumen is parallel to and radially offsetfrom the cooling element.

Preferably, said cooling element is arranged within the balloon so that,in use, the inner surface of the balloon is cooled substantiallyuniformly by the cooling element around the circumference of theballoon.

Preferably, the elongate cooling element extends along a longitudinalaxis in a direction parallel to a central axis of the balloon.

Preferably, the central axis of the balloon is radially offset from thelongitudinal axis of the elongate cooling element by 0.1 to 0.5 mm, morepreferably 0.2 to 0.4 mm.

Preferably, the cooling element is arranged inside the flexible heattransfer element such that, when viewed in the plane normal to thelongitudinal axis of the cooling element, the cooling element isprovided substantially within the centre of the balloon.

Preferably, the flexible heat transfer member is configured to inflateanisotropically when viewed in the plane normal to the longitudinal axisof the cooling element so as to form the balloon.

Preferably, the flexible heat transfer element is configured to inflateinto a substantially cylindrical balloon having first and secondasymmetric ends.

Preferably, the conduit arranged to supply an inflation fluid, the guidewire lumen and the elongate cooling element are provided inside a shaft,wherein the flexible heat transfer element is adhered to the shaft atthe first end, and wherein the flexible heat transfer element is adheredto the guide wire lumen at the second end.

Preferably, said cooling element comprises a first tube provided insidea second tube, wherein the first tube is substantially parallel to thesecond tube; and the second tube is configured to receive a flow of acoolant for cooling the cooling element from the first tube.

Preferably, in use, the first tube and the second tube are operated suchthat the pressure of the second tube is lower than the first tube.

Preferably, said cooling element comprises an elongate cooling chamberconfigured to receive coolant from the first tube and provide saidcoolant to the second tube.

Preferably, the elongate cooling chamber is arranged co-linearly with anend of the second tube.

Preferably, said cooling element further comprises a restriction tubeconfigured to convey the coolant from the first tube to the coolingchamber, wherein said restriction tube has narrower internal diameterthan the first tube.

Preferably, the restriction tube and cooling chamber are configured suchthat when the coolant conveyed along the first tube as a liquid, atleast some of the coolant undergoes a phase change in the restrictiontube and/or in the cooling chamber and returns through the second tubeas a gas.

Preferably, said balloon is substantially cylindrical.

Preferably, in use in a vessel, the inflated flexible heat transferelement occludes fluid flow between the walls of the vessel and theinflated flexible heat transfer element.

Preferably, the conduit is further configured to provide a return flowof the inflation fluid of the flexible heat transfer element.

Preferably, the conduit comprises; a third tube for providing a supplyflow of the inflation fluid of the flexible heat transfer element; and afourth tube for providing a return flow of the inflation fluid of theflexible heat transfer element.

Preferably, said cooling element is not attached to the end of the guidewire lumen and wherein said cooling element is configured such that,when in use, the flow of the coolant causes the cooling element tovibrate.

Preferably, the flexible heat transfer element has single walled outermembrane.

Preferably the catheter further comprises a heater for heating theinflation fluid, or solidified inflation fluid, of the flexible heattransfer element.

Preferably, the conduit, the guide wire lumen and the cooling elementprotrude from a shaft, wherein, inside the shaft, the cooling elementhas an outer surface having a flattened-circular shape when viewed inthe plane normal to the longitudinal axis of the cooling element.

Preferably the conduit, the guide wire lumen and the cooling elementprotrude from a shaft, the shaft comprising a solid body occupying theregions between the conduit, the guide wire lumen and the coolingelement.

LIST OF FIGURES

Embodiments of the invention will now be discussed with reference to theaccompanying drawings in which:

FIG. 1 is a schematic illustration of a cross section of a coolingelement of a catheter according to an embodiment;

FIG. 2 is a schematic illustration of a cooling element of a catheteraccording to an embodiment;

FIG. 3 is a schematic illustration of a cross section of a coolingelement of a catheter according to an embodiment;

FIG. 4 is a schematic illustration of the distal end of a catheteraccording to an embodiment;

FIG. 5 is a schematic illustration of a cross section of the distal endof a catheter according to an embodiment;

FIG. 6 is an illustration of a system for operating a catheter accordingto an embodiment.

DESCRIPTION OF EMBODIMENTS

There is a motivation in known balloon catheters, in particular that ofWO'414, to position the guide wire lumen (GWL) centrally within theshaft and the balloon to ease the insertion of the catheter into a body,and simplify the manufacturing process. Since the GWL is centrallydisposed within the balloon, the cooling element must be providedoff-centre, as viewed in a plane normal to the longitudinal axis of thecooling element. Due to the thermal resistance of the fluid which isinside the balloon when the balloon is inflated, areas of the surface ofthe balloon which are further from the cooling tube will not be cooledas quickly or effectively as those which are nearer the cooling tube.The surface of the balloon and any surrounding tissue will thereforecool unevenly.

Embodiments of the invention provide a new and advantageous design ofballoon catheter. The new design of catheter overcomes the above problemof uneven cooling by arranging the cooling element and the GWL insidethe flexible heat transfer element, such that, when inflated, thecooling element is substantially central within the balloon and the GWLis parallel to and radially offset from the cooling element. Spatialvariations in heat transfer across the balloon are hence reduced,thereby enabling improved cryotherapy. Further still, the advantages ofthe cooling elements disclosed in WO'414 may be retained. The catheterdesign has a wide range of applications, particularly in the field ofcoronary vascular diseases, which may include plaque stabilisation. Ofcourse, the size of the catheter may be adjusted depending on theapplication and thus the catheter is also in principle suitable forother applications including atrial fibrillation, the treatment of renaldenervation and tumour ablation.

The catheter is a balloon catheter and comprises a plurality of lumenssupported inside a common shaft, except for in a balloon region wherethey are instead provided within a flexible heat transfer element. Theflexible heat transfer element is configured to be inflated to form aballoon. One or more lumens are provided inside the shaft for providinga supply and return of inflation fluid to the balloon, as well as thecooling element for cooling the inflation fluid. The cooling elementextends from the shaft and is preferably unsupported within the balloonbut embodiments also include the cooling element being attached to theGWL.

The cooling element is elongate and typically substantially cylindrical,comprising tubular walls. The cooling element also preferably comprisesfirst and second tubes for providing supply and return paths of acoolant, wherein the first tube (which is also referred to herein as thesupply lumen) is provided inside a larger second tube (which is alsoreferred to herein as the return lumen). The first tube and the secondtube are each elongate and extend along axes that are substantiallyparallel to one another. The distal tip of the return lumen may beclosed, whereas the distal tip of the supply lumen may be open and stopshort of the end of the return lumen such that coolant may flow from thesupply lumen in a first direction into the return lumen, and then flowin a second direction, opposite to the first direction, back along thereturn lumen. When the coolant flows from the supply lumen to the returnlumen it moves into a region of increased volume and consequentlyreduces in pressure. This causes a phase change in the coolant, whereinat least some of the coolant will evaporate, causing the temperature ofthe cooling element to reduce.

The one or more lumens that provide supply and return flows of a fluidfor inflating the balloon are preferably completely separate from thelumens used to supply the coolant. The inflation of the balloon and thecooling of the cooling element are preferably performed by separatemechanisms and these operations can be controlled and operatedindependently of each other.

The catheter may also contain a means for heating the inflation fluidwithin the balloon. This could be used, for example, if the inflationfluid froze during treatment and it was necessary to rapidly thaw theinflation fluid. The ability to induce such rapid thawing isparticularly beneficial in case the catheter needs to be removed from anartery quickly, for example in emergency situations. The heat could beprovided by any type of heater, for example a small electric heater,such as a resistor, positioned inside the balloon but outside thecooling element and supplied by an electric current via wires runningdown the catheter shaft. The heater element could be formed by a thinfilm resistor printed on the outer surface of the cooling element, adiscrete resistor positioned inside the balloon, or by the inflationfluid itself. In the case where the inflation fluid forms the heaterelement, wires would supply electricity to electrodes at the proximaland distal ends of the balloon and terminate there, in contact with theinflation fluid, so that an AC or DC current could be passed through theinflation fluid inside the balloon, causing it to warm up.

In use, the catheter is inserted into a body such that the balloonregion is positioned next to a region of tissue to be cooled in avessel. For example, if the catheter is used instead for plaquestabilisation by cryotherapy, the balloon region may be positioned nextto the plaque. The catheter's balloon is inflated by a liquid and theouter surface of the balloon comes into thermal contact with the tissue.Coolant is supplied to the cooling element and the temperature of thecooling element reduces. The inflation liquid within the ballooncontacts the outer surface of the cooling element and is thereby cooled.It is important to remove all gas from the balloon prior to inflating,as gas bubbles in the balloon will have an impact on the heat conductionthrough the balloon. This is typically performed using a vacuum pump orsyringe before the catheter is inserted into the body. However it mayalternatively be performed in vivo.

An advantageous aspect of the above-described catheter design is thatthe coolant of the cooling element is not the same as the fluid used toinflate the balloon. The cooling element can safely support a phasechange of the coolant since the cooling element is closed. Since thecoolant is not in fluid communication with the inflatable flexible heattransfer membrane, there is little chance of it leaking from thecatheter into a blood vessel and so the requirement to have a doublelayered balloon may be avoided. A single layered balloon issignificantly more maneuverable and streamlined than a balloon withmultiple membranes. Moreover, the catheter design is simpler than knowndesigns employing a double balloon system and this reduces costs andmanufacturing complexity.

The arrangement of the coolant supply lumen inside the coolant returnlumen allows for the cooling element to maintain a small cross sectionalarea. This, in combination with the fact that only one cooling elementis required, enables the catheter (in particular the shaft) to maintaina small diameter. This makes it particularly suitable for applicationsin small diameter arteries, such as in the coronary or smallerperipheral vasculature, where known catheter designs are difficult toinsert and/or manoeuvre.

A further benefit of the preferred cooling element design is thatcooling due to the phase change occurs in a clearly defined locationthat can be controlled as required. This improves the efficiency of thecatheter system since the lumens that deliver coolant do not need tohave high levels of insulation between the coolant and the surroundingenvironment. Moreover, the parallel arrangement of supply and returnlumens means that the liquid coolant is kept cool by the cold, gaseouscoolant returning from the distal tip of the catheter. This helpsprevent the liquid coolant from boiling as it flows into that part ofthe catheter which is inside the body (and therefore at 37° C.).

The cooling element and the guide wire lumen are arranged inside theflexible heat transfer element such that, when inflated the coolingelement is substantially central within the balloon and the guide wirelumen is parallel to and radially offset from the cooling element. Thecentral axis of the balloon will typically extend through the elongatecooling element, in the direction of the longitudinal axis of thecooling element. In embodiments where the balloon is elongate, forexample, substantially cylindrical, the central axis of the balloon isalso the major axis of the balloon.

The longitudinal axis of the cooling element is generally not exactlythe same as the central axis of the balloon. It is advantageous toarrange the cooling element so that the thermal resistance between thecooling element and the surface of the balloon is uniform in all radialdirections (i.e. all directions perpendicular to the longitudinal axisof the cooling element). In order to compensate for the presence of theGWL (and any other lumen that may be provided inside the balloon), thismay mean that the cooling tube is not exactly centred inside theballoon. The cooling element is therefore only ‘substantially central’within the balloon. In some embodiments the longitudinal axis of thecooling element may be distally offset from the central axis of theballoon by anything from 0 to 33% of the radius of the balloon, moretypically 0 to 20%. For example, for a cylindrical 3 mm diameter balloonhaving a 1 mm diameter cooling element, the centre of the coolingelement may be up to 0.5 mm offset from the centre of the balloon, asviewed in a plane normal to the longitudinal axis of the coolingelement. The exact position of the cooling element within the balloonmay vary slightly during use as the cooling element may be free tovibrate inside the balloon. However the arrangement of the coolingelement relative to the GWL should remain the same.

Further advantages of embodiments are set out in the detaileddescription provided below.

FIG. 1 shows a cross section of the design of a cooling element 105 of acatheter according to an embodiment. On the left hand side of FIG. 1 areshown the tubular supply lumen 102 and the tubular return lumen 101 ofthe coolant. The supply lumen 102 is positioned inside the return lumen101 in a substantially co-axial configuration. An end of the supplylumen 102 is connected to, and in fluid communication with, arestriction tube 103. The restriction tube 103 has a narrower diameterthan the supply lumen 102. The other end of the return lumen 101 to thatconnected to the supply lumen 102 ends in a cylindrical cooling chamber104 of cooling element 105. In the present embodiment, the coolingchamber 104 has a slightly larger diameter than the return lumen 101 andextends over the outside of the return lumen 101.

In use, a flow of pressurised coolant is input to the supply lumen 102.The coolant may be a liquid or a mixture of a liquid and a gaseous formof the coolant. The restriction tube 103 at the end of the supply lumen102 ensures that there is little pressure drop within the supply lumen102 and so most, or all, of the pressurised liquid coolant remains inthe liquid phase in the supply lumen 102. Along the length of therestriction tube 103, the pressure drops from a maximum value at theconnection to the supply lumen 102 to a lower pressure at the exit ofthe restriction tube 103 into the cooling chamber 104. When the liquidcoolant flows into the restriction tube 103 the pressure drop caused bythe restriction means that the pressure of the liquid falls below itsvapour pressure at the temperature of its surroundings at that point.This causes at least some of the liquid coolant to evaporate and undergoa phase change into a gas. Liquid coolant that flows from therestriction tube 103 into the cooling chamber 104 will also expand andmay evaporate within the cooling chamber 104 and/or return lumen 101.The expansion of the coolant, and the phase change of the coolant, has acooling effect on the walls of the cooling chamber 104. The coolant thenflows from the cooling chamber 104, in liquid and/or gaseous form,through the return lumen 101. The pressure within the return lumen 101,and thereby the cooling chamber 104, is preferably reduced by a vacuumpump. The vacuum pump, described in more detail later, operates on theother end of the return lumen 101 to that connected to the coolingelement 105. The reduction of pressure both increases the cooling effectdue to expansion and phase change of the coolant and ensures that thecoolant in the cooling chamber 104 flows into the return lumen 101.

FIG. 2 shows a perspective of the cooling element 105 of FIG. 1. Thecooling chamber 104 has a slightly larger diameter than the return lumen101. A greater cooling effect is achieved since more coolant willundergo a phase change in the cooling chamber 104. In addition, theouter diameter of the cooling chamber 104 has a larger surface area andis therefore more effective at cooling the inflation fluid.

Preferably the lumens of the cooling element are made of reasonablystrong materials so that they can withstand the pressure of apressurised coolant. In some embodiments these lumens also have a degreeof flexibility so that the catheter can deform to match the profile ofan artery.

The supply lumen 102, return lumen 101 and restriction tube 103 may bemade of nylon, tri-layered tubing, polyimide, PEBAX™, such as PEBAX 55D,or other suitable materials. The supply lumen 102 and return lumen 101may also be metal or polymer braided to add extra strength and flexibleproperties. The restriction tube 103 and supply lumen 102 may be made atthe same time so that they are integral with each other, or they may beconstructed as separate components and then glued together. Furthermorethe cooling chamber 104 may be made entirely, or in part, of copper sothat the cooling chamber 104 has good thermal conductivity properties.Alternatively, the entirety of the cooling element 105 may be made frompolyimide, as this material is strong, enabling the walls to be madeextremely thin. Using the same material throughout the cooling element105 also improves the ease of manufacture of said cooling element.

Preferably, the coolant is N₂O and enters the restriction tube 103 withsubstantially all of the coolant being in the liquid phase. The coolantmay exit the restriction tube 103 with some of the N₂O being in theliquid phase and some of the N₂O being in the gas phase. Preferably,most of the N₂O is in the liquid phase.

The embodiment shown in FIG. 3 differs from that shown in FIG. 1 in thatthe cooling chamber 301 of the cooling element 302 has the same innerand outer diameters as the return lumen 101. The cooling chamber 301 isstill closed, i.e. blocked, at the other end to that connected to thereturn lumen 101. The dimensions and materials of the return lumen 101,supply lumen 102 and restriction tube 103 may be the same as describedabove with reference to FIGS. 1 and 2. The length of the cooling chamber301 from the end of the restriction tube 103 to the closed end of thecooling chamber 301 is preferably 1 mm to 15 mm. Advantageously, thecooling chamber 301 is narrower than that shown in FIGS. 1 and 2.

The presence of a restriction tube 103 and a distinct cooling chamber104 is optional however. In alternative embodiments, the liquid coolantmay flow directly from the supply lumen 102, into the return lumen 101,either through the distal tip (i.e. end) of the supply lumen 102 orthrough one or more apertures in the wall of supply lumen 102,distributed along its length. In this case, some of the coolant mayundergo a phase change when moving to enter the return lumen 101, whichhas a lower pressure than the supply lumen 102. This lower pressure maybe achieved by ensuring that the annular internal volume of the returnlumen 101 is larger than the internal volume of the supply lumen 102and/or by using a vacuum pump.

FIG. 4 is a perspective view of a catheter 10 according to anembodiment. The catheter 10 comprises a hollow tubular shaft 2 whichextends along the length of the catheter and envelops the lumensprovided within except in a balloon region 1, where an inflatableflexible heat transfer member 16 is provided. The shaft 2 is made ofpolyether block amide as braided, or unbraided, PEBAX™, such as PEBAX55D, and is formed using extrusion or a heat reflow process.

The interior of the shaft 2 comprises a conduit 18, an elongate,cylindrical cooling element 11 and a cylindrical guide wire lumen (GWL)17. The cooling element 11 may be similar to any of the embodimentsdescribed in FIGS. 1 to 3 and comprises a supply lumen 102 providedinside a return lumen 101.

The cooling element is provided within an inflatable heat transferelement in the form of a membrane 16 that is configured to be inflatedinto a balloon 70. The cooling element extends along the longitudinalaxis of the balloon 16 in a straight line until it terminates near thedistal end of the balloon, preferably approximately midway along thedistal half of the balloon region 1. The cooling element 11 is centrallyarranged and the flexible heat transfer member 16 shaped such that, whenthe balloon 70 is inflated, a substantially even cooling distribution isapplied across the balloon 70. In particular the cooling element 11 andthe guide wire lumen (GWL) are arranged such that the outside of theballoon 70 (i.e. the surface of the inflatable heat transfer membrane16) is cooled quickly and uniformly. This is later discussed in moredetail in connection with FIG. 5.

The GWL 17 is configured to be threaded over a surgically implantedguide wire 15 (shown in FIG. 5), when in use, for positioning thecatheter 10 inside a patient. The GWL 17 extends from the guide wireentrance aperture at the distal tip of the catheter 10, to a guide wireexit aperture provided on the shaft 2 (as is standard for Rapid Exchangecatheters). Alternatively, an ‘over the wire’ configuration may be used.The GWL 17 is a hollow tube and is made of tri-layer or a similarmaterial.

The inflatable heat transfer membrane 16 is adhered to the distal tip ofthe shaft 2 on its proximal end and the GWL 17 on its distal end. Thecentral region between these two ends is configured to be inflated intoa substantially elongate, and substantially cylindrical balloon 70.Although the schematic illustration of FIG. 4 shows the membrane 16 toextend from the shaft 2 at the proximal end of the balloon region 1 at asharp, constant angle up towards a cylindrical region (and back fromthis region towards the GWL 17 at the distal end), it should beunderstood that this profile is typically tapered, with the shape beingprimarily dictated by the elasticity and shape of the flexible heattransfer membrane 16, rather than any internal supporting members. Theangle at which the membrane 16 extends from the shaft 2 at the proximalend of the balloon region 1 and later adjoins onto to the GWL 17 at thedistal end of the balloon region 1 varies about the longitudinal axis 60of the cooling element 11 (and the central axis 50 of the balloon). Thisensures that the cooling element 11 is located centrally within theballoon 70, as is evident by FIG. 4. This means that although thecentral region of the balloon 70 is substantially uniform andcylindrical, the tapered end regions are asymmetric.

Embodiments also include the inflated balloon alternatively beingsubstantially spherical. A degree of asymmetry may be introduced howeverin order to achieve central positioning of the cooling element insidethe balloon. The conduit 18 (referred to herein as the inflation lumen)is provided for supplying an inflation fluid for inflating the flexibleheat transfer membrane 16 so as to form the inflated balloon 70. Theinflation lumen 18 extends along the inside of the shaft 2 and, in thisembodiment, protrudes from the shaft 2 into the balloon region 1.Alternatively however the inflation lumen may terminate at the end ofthe shaft 2. In some embodiments a plurality of said inflation lumensmay be provided in order to allow faster inflation or to reduce theoverall cross sectional area of the shaft 4 since in some instance twoor more small inflation lumens may be physically easier to accommodateinside the shaft 2 than one large inflation lumen.

The shaft 2, and in particular, the space between the lumens providedinside the shaft 2, may act as a return path for providing a flow ofinflation fluid from the balloon 70 back along the shaft 2 in a reversedirection to the flow of inflation fluid in the inflation lumen 18. Thisenables space savings inside the shaft 2 since it is not necessary toprovide a separate deflation tube. Alternatively, the flow direction ofthe inflation fluid may be reversed such that the conduit 18 behaves asa deflation lumen whilst the shaft 2 behaves as an inflation lumen.Furthermore the shaft 2 and/or inflation lumen 18 may function as bothan inflation and deflation lumen in some circumstances, in which casethe pressure is simply reversed at one end of the shaft 2 and/orinflation lumen 18.

It is desirable to provide a shaft 2 having a small diameter so as toallow the catheter to more readily fit through small vessels. In anembodiment this may be achieved using a process called ‘reflow’ wherethe outer wall of the shaft 2 is extruded around the inner lumens of theshaft 2 (comprising the inflation lumen 18, GWL, the cooling element 11and optionally a separate deflation lumen), so as to form a solid bodycompletely filling the space between the inner lumens and the outsidesurface thereby joining the inner lumens together. This compositeconstruction allows for a reduced thickness of the wall of the reflowedshaft beyond what it would be if the shaft were provided in the form ofa separate tube surrounding the inner lumens. Typically this reductionis equivalent to the thickness of the outer tube of a shaft 5, which maybe between 0.1-0.3 mm.

In an alternative embodiment the overall diameter of the shaft 2 may bereduced by providing a cooling element 11 having an outer surface in theform of a flattened circle, such as an oval or an ellipse, as viewed ina plane normal to the longitudinal axis of the cooling element 11,across the shaft 2. In this case, the remaining lumens which extendalong the inside of the shaft 2 may be arranged around the smaller outerdiameter of the cooling element 11. This enables a shaft 2 in the formof a tube having a smaller diameter than would otherwise be possible tobe used to tightly surround the inner lumens. The return lumen 101 ofthe cooling element 11 may be formed so as to maintain itsflattened-circular shape section along its length (including the portionprotruding from the shaft 2). Alternatively the return lumen 101 may beformed of a compliant material which deforms inside the shaft 2 so as toform the flattened-circular inside the shaft, whilst maintaining acircular cross-section outside of the shaft 2.

In an embodiment, the cooling element 11 is attached to the GWL 17inside the balloon region 1. However, in a preferred embodiment, thecooling element 11 is not attached to the GWL 17 inside the balloonregion 1 and so the cooling chamber is free to vibrate, i.e. movelaterally with respect to the longitudinal axis of the GWL 17.

The closed distal end of the return lumen may typically extendapproximately an additional 2.0 to 3.0 mm from the open distal end ofthe supply lumen. This region could be thought of as the cooling chamber104.

The following dimensions may be desirable for certain applications thatmay include the treatment of plaque stabilization and atrialfibrillation on a human or animal:

-   -   Cooling element 11        -   Outer diameter=0.35 to 1.0 mm        -   Outer wall thickness=0.019 to 0.05 mm        -   Length=15 to 30 mm    -   Return lumen 101        -   Outer diameter=0.35 to 1.0 mm        -   Outer wall thickness=0.019 to 0.05 mm        -   Length=1000 to 1750 mm    -   Supply lumen 102        -   Outer diameter=0.12 to 0.4 mm        -   Outer wall thickness=0.014 to 0.05 mm        -   Length=1000 to 1750 mm    -   Restriction tube 103        -   Outer diameter=0.0762 to 0.140 mm        -   Outer wall thickness=0.019 to 0.0254 mm        -   Length=5 to 50.8 mm    -   Inflation lumen 18        -   Outer diameter=0.254 to 0.406 mm        -   Outer wall thickness=0.0191 to 0.0508 mm        -   Length=1000 to 1750 mm    -   GWL 17        -   Outer diameter=0.40 to 1.0 mm        -   Inner diameter=0.35 to 0.95 mm        -   Length=650 mm    -   Shaft 2        -   Diameter=1.35 to 3.3 mm

Embodiments also include other dimensions, in particular the dimensionsas provided in WO'414 which are incorporated herein by reference, andthe above dimensions may be scaled up or down so that the catheter canbe used with vessels of any size.

The cooling element is encompassed by the balloon 70. That is to say, inuse the cooling element 11 is within the inflation fluid of the balloon70 and there is no membrane of the balloon 70 arranged between theinflation fluid and the cooling element 11.

The balloon 70 is typically 15 mm to 30 mm long and, when deflated, ispreferably substantially flush with the outer surface of the shaft 2 sothat the outer diameter of the catheter is not increased by the deflatedballoon. For example, the outer diameter of the catheter may besubstantially 4 Fr (i.e. 1.333 mm). When inflated, the outer diameter ofthe balloon 70 may be 2.5 mm to 4 mm. A larger balloon 70 may berequired in the treatment of atrial fibrillation however with a diameterof approximately 24 mm (e.g. +/−10%). The dimensions of the cathetercomponents, such as the lumen, may be adjusted depending on theapplication and, in particular, the size which the balloon is configuredto be inflated. For example, larger lumen may be desired in order toinflate and deflate a large balloon more quickly, or apply an increasedcooling effect.

The balloon 70 may be made of a variety of materials and is desirablycompliant or semi-compliant to ensure a good fit with the target areafor effective heat exchange and a more even temperature distributionaround the tissue. The balloon 70 may also be non-compliant if this isappropriate for the desired application. The balloon design andconstruction may be as known in the art of balloon angioplasty. However,there is no need for the balloons to be as strong, and with as thickmembranes, as those used for angioplasty since the inflation pressuresused in embodiments are substantially lower than those used inangioplasty. This is because the balloons are not required to enlargethe vessel. The balloons in embodiments are only required to make a goodthermal contact with the vessel and the balloons are thereforepreferably made with a thinner membrane than balloons used forangioplasty. The balloons can be made of a variety of materials such assilicone or polyurethane for compliant balloons and nylon or polyesterfor non-complaint balloons. Wall thickness will also vary depending onthe properties to be achieved and are generally in the range of 5 to 100microns. The balloon may also have a substantially smooth exteriorsurface so that heat transfer is optimised from the tissue on theinterior surface of the vessel. The balloon material and thickness maybe optimised to minimize thermal losses through the balloon wall.

The balloon 70 may also be formed from a membrane 16 which is shaped,stretched or otherwise configured such that the balloon 70 inflatesanisotropically (i.e. asymmetrically) when viewed in the plane normal tothe longitudinal axis of the cooling element. In other words, theballoon 70 may radially expand from the GWL 17 onto which it is securedby different amounts so as to ensure that the cooling element 11 issubstantially central within the balloon 70. An example of this is shownin FIG. 4 where the region A of the balloon 70 that extends between theGWL 17 and an upper surface E of the balloon 70 is greater than theregion B which extends between the GWL 17 and a lower surface F of theballoon 70. In the embodiment of FIGS. 4 and 5 the range A extends 2.3mm radially, whereas distance B extends 0.2 mm radially, as is evidentfrom the scale on FIG. 5.

In use, an inflation fluid is supplied to the inflation lumen 18 toinflate the balloon 70. The cooling element 11 is then cooled by theexpansion and/or evaporation of the coolant as described in the aboveembodiments. The flow of the coolant that may be a liquid and/or gas,from the supply lumen 102 to the return lumen 101 (potentially via arestriction lumen and cooling chamber, if provided) causes the distalend of the cooling element, if it is not fixed to the GWL 17, tovibrate. Advantageously, this vibration movement of the cooling element105 increases the agitation of the inflation fluid and thereby the flowover and around the cooling chambers 104 and thereby both increases therate at which the inflation fluid is cooled and the temperatureuniformity of the inflation fluid. The inflation fluid is in contactwith the inner surface of the balloon 70 and the balloon 70 is therebycooled as the inflation fluid is cooled. The outer surface of theballoon 70 is therefore cooled due to the cooling of the inflation fluidby the cooling element. When an operator determines that sufficientcooling has been applied by the catheter, the balloon 70 is deflatedusing the deflation lumen and the catheter can then be removed.

The catheter could alternatively be realised with the cooling element 11being fixed to the GWL 17. However, this will help maintain the relativeposition of the cooling element to the balloon. The vibration of theballoon may be reduced from if the cooling element was not fixed to theGWL, but the vibration is preferably not entirely prevented.

Preferably the inflation fluid has a fixed volume. This limits anydamage caused by any leakage of the inflation fluid from the catheter.Any leakage of the inflation fluid can also be detected by monitoringthe pressure of the inflation fluid when the balloon 70 is inflated orby determining if the amount of inflation fluid after a procedure is thesame as that at the start of the procedure.

The inflation fluid is preferably a liquid so that even if there is aleakage from the catheter, the leakage is of a liquid and not a gas. Theinflation fluid may be a solution that comprises sodium chloride, suchas saline, with a sodium chloride concentration of about 0.9%, or asolution with a higher concentration of sodium chloride, preferably a25% concentration of sodium chloride. The inflation fluid is preferablywater based, and may include various additives to lower the freezingpoint. Additives may include one or more of sodium chloride, calciumchloride, ammonia, ethanol, propylene glycol, ethylene glycol, propanoneand butanone. Other additives may also be used, including contrastmedia. The inflation fluid is also preferably sterile. To ensure thatthe inflation fluid is sterile, the inflation fluid may be provided froma separate container, such as a pre-packed bag or syringe that isconnected to the catheter.

The same apparatus for supplying the inflation fluid to into theinflation lumen 18 may have its operation reversed so that it is alsoable to deflate the balloon 70 by removing the inflation fluid. Forexample the inflation fluid may be injected into the lumen 18 by anoperator pressing on the plunger of a syringe. The same syringe can alsobe used to remove the inflation fluid by the operator withdrawing theplunger. Advantageously, such an arrangement allows an operator toeasily determine if any of the inflation fluid has leaked from thecatheter by checking for entrained air bubbles or blood in the inflationcircuit following plunger withdrawal.

FIG. 5 is a cross-sectional view of the catheter of FIG. 4 taken throughthe X-X′ plane. The arrangement of the cooling element 11 and the GWL 17relative to the central (i.e. ‘longitudinal’ or ‘major’) axis 50 of theballoon 70 is schematically illustrated. The cooling element 11comprises a supply lumen 102 co-axially arranged inside a return lumen101, as previously described. The cooling element 11 extends along itslongitudinal axis 60 in a direction parallel to the central axis 50 ofthe balloon 70. The longitudinal axis 60 is displaced from the centralaxis 50 by a distance d in a radial direction (perpendicular to axes 50and 60). The cooling element 11 is still arranged substantiallycentrally within the balloon 70 however, with the central axis 50 of theballoon 70 extending through the cooling element 11. In this case thecentral axis 50 extends through the annular region between the supplylumen 101 and the return lumen 102. In other embodiments the centralaxis 50 of the balloon 70 may extend through the supply lumen 101. Thelongitudinal axis 60 is typically radially offset from the central axis50 by less than 0.5 mm, more typically between 0.1 to 0.4 mm.

The distance of separation d between the central axis 50 of the balloon70 and the longitudinal axis 60 of the cooling element 11 is chosen suchthat, when the cooling element 11 cools the surrounding inflation fluid,the increased thermal resistance of the GWL 17 relative to the inflationfluid is compensated for such that the surface of the balloon 70 iscooled uniformly (including, the opposing edges E and F).

The GWL 17 is provided substantially off-centre with respect to theballoon 70 such that the central axis 50 does not extend through theGWL. The outside of the GWL 17 is typically radially offset from thecentral axis 50 by at least 0.5 mm, more preferably 0.5 to 1.8 mm.

A scale is also shown in FIG. 5 to illustrate an example of a possiblearrangement in accordance with an embodiment. The scale runs fromopposing edges E and F of the balloon 70. In this embodiment a 3 mmdiameter inflated balloon 70 encases a cooling element 11 having a 0.4mm diameter supply lumen 102 provided inside a 1.0 mm diameter returnlumen 101. Also provided is a 0.5 mm diameter GWL 17. As shown, thereturn lumen 101 extends 1.3 mm to 2.3 mm from edge E and has itslongitudinal axis 60 at a distance 1.8 mm from the edge of the balloon70. The balloon has a radius of 1.5 mm and so the distance d between thecentral axis 50 of the balloon 70 and the longitudinal axis 60 of thecooling element 11 in this case is 0.3 mm. In other embodiments thisseparation may be between 0.1 to 0.5 mm, more preferably 0.2 to 0.4 mm.

As viewed in FIG. 5, the GWL 17 extends approximately 2.3 mm to 2.8 mmfrom the edge E such that it is in contact with the outside of thecooling element 11. An inflation fluid surrounds the outside of thecooling element 11 and the GWL 17, filling the remaining volume showninside the balloon 70, including in the region 2.8 mm to 3.0 mm betweenthe outside of the GWL 17 and the balloon 70. In alternative embodimentsthe GWL 17 may be at least partially in contact with the flexible heattransfer membrane 16 which forms the surface of the balloon 70, howeverpreferably the GWL 17 is not attached to the membrane 16.

FIG. 6 is an illustration of an exemplary system for using the catheteraccording to the embodiments described herein to cool a target part of avessel. It will be understood that some of the specifically describedcomponents may not be essential to the operation of the system but aredescribed for context only. Suitable, functionally similar, orequivalent components may be used interchangeably.

The system comprises:

-   -   Coolant cylinder 1001    -   Pressure regulator 1002    -   Tri-connector 1004    -   Vacuum pump 1005    -   Inflation device 1003    -   Catheter shaft 1006

Although not shown in FIG. 6, the system also comprises a catheter endaccording to any of the embodiments described herein.

The coolant cylinder 1001 has a dip tube and spigot valve forcontrolling the supply of the coolant. A flexible high pressure hoseconnects the coolant cylinder to the pressure regulator 1002. Aninjection tube from the pressure regulator connects to the tri-connector1004. Also connected to the tri-connector is an inflation tube connectedto inflation device 1003 and a vacuum tube connected to the vacuum pump1005. The tri-connector maintains the injection tube, the vacuum tubeand the inflation tube as separate from each other. The tri-connectoralso connects to the catheter shaft 1006 and thereby supports fluidand/or gas communication between the catheter and the coolant supply,vacuum pump, and inflation device.

The system may also include a heat exchanger, not shown in FIG. 6, tocool the liquid coolant before it enters the catheter. This will preventboiling of the coolant as it enters the warm environment of thepatient's body. Heat may be removed from the liquid coolant by using arefrigeration circuit or Peltier cooler.

The system may further comprise a computer, such that the system may besoftware controlled, the computer having one or more controls and/or auser interface such as a graphical user interface. The system may alsofurther include assemblies for temperature and/or pressure monitoringbased on signals received from one or more sensors.

The inflation device 1003 operates by causing an inflation fluid to flowinto the catheter shaft 1006 when the plunger is pressed. The inflationdevice is also a deflation device since the inflation fluid flows backinto the device from the catheter when the plunger is withdrawn. Theinflation device may alternatively be an electric pump.

The vacuum pump 1005, that may be an electric vacuum pump, operates onthe return lumens of the coolant. The vacuum pump 1005 advantageouslylowers the pressure in the return lumen and/or cooling chamber of thecooling elements to thereby increase the amount of phase change of thecoolant that occurs. The vacuum pump 1005 also ensures that the coolantin the supply lumens and cooling chambers (where provided) flows intothe return lumen.

A further advantage applying the vacuum pump 1005 to the return lumensis that the pressure in the return lumen is relatively low and less thantypical blood pressure in a body. In use, should the return lumens leak,this would result in blood flowing into the return lumens rather thanthe coolant flowing out. The vacuum pump 1005 thereby improves thesafety of the catheter.

The system may also comprise a deflation device, separate from theinflation device 1003, that is in fluid communication with the cathetershaft 1006 through an additional separate connection to thetri-connector. The deflation device may be a vacuum pump, such as anelectric vacuum pump.

Variables that influence the operation of the catheter are the pressureof the inflated balloon and the temperature of the outer surface of theballoon. Both of these are controllable by how the system of FIG. 6 isoperated. The pressure of the balloon is controllable by controlling theamount, and pressure of, the inflation fluid by inflation device 1003.The temperature of the outer surface of the balloon is dependent on boththe temperature of the cooling element, and how long the cooling elementhas been cooling the inflation fluid. The temperature of the coolingelement is controllable by controlling the pressure and the amount ofcoolant that flows into the catheter. The length of time that theinflation fluid is cooled by the cooling element is easily controlled bywhen the system operator starts and stops the flow of the coolant intothe catheter.

Preferably, the pressure of the balloon is maintained at lower than 5ATM (507 kPa), typically between 3.5 ATM (355 kPa) to 4.5 ATM (456 kPA),but may be as low as 3 ATM (304 kPa) or 1 ATM (101 kPa). It may bedesirable for the balloon pressure to be as low as possible foreffective treatment in order to mitigate the risk of a reactionoccurring in the blood vessel that leads to re-stenosis or blockage. Ashort-term response to the application of high-pressure cryotherapy isalso often smooth muscle cell proliferation, which is potentiallydangerous. The tissue interface temperature is preferably maintainedwithin a desired range in order to remove heat from the plaque andvessel without significantly ablating the cells. It is noted thatthroughout the present document, all pressures given as gauge pressures,that is, above atmospheric pressure.

The temperature of the outer surface of the balloon is maintained withinappropriate ranges given the application. For example, for cryotherapy,the temperature is preferably maintained between +15° C. (288K) and −35°C. (238K) and more preferably between 0 to −30° C. (273K to 243K). Foratrial fibrillation (and other applications where tissue ablation isrequired) the temperature may be much lower, for example between −50° C.to −90° C. (223K to 183K), although typically around −80° C. (193K).

The exact temperature will depend on the treatment application,according to standard practice. Depending on the type of balloon and theheat load, there may be a temperature difference of about 10° C. to 40°C. between inner and outer balloon temperature and this can becompensated for when controlling the system.

Preferably, sensors are provided within, on or near the catheter end,such as on or just inside the balloon, in order to monitor and therebycontrol the temperatures and pressures in a feedback control system. Forexample, a thermocouple may be fixed to the GWL or coolant return tubeto measure the temperature inside the balloon. One or more furtherthermocouples may be attached to the internal or external surface of theballoon in order to measure the balloon tissue interface temperature. Inaddition, a pressure sensor may be placed inside the balloon toaccurately monitor and thereby control the pressure within the balloon.The pressure sensor may be an open hydraulic tube with no flow, or maybe positioned on the inflation circuit near the inflator, so that thefluid pressure inside the tube is measured outside the catheter. Thepressure sensor may also be a piezoelectric transducer, fibre-optictransducer or other type of sensor. Pressure sensors and a flow metermay also be positioned in the coolant circuit, to measure the pressureand flow of the coolant.

Both temperature and pressure signals can be used to control refrigerantflow such that balloon pressure and/or surface temperature remain withinthe desired ranges. The pressure transducer may also be used to detectany leaks within the catheter by sensing abnormal pressures. Thetemperature sensor(s) may also be used to detect vessel occlusion by theballoon.

As described earlier, the catheter may also comprise means for heatingthe inflation fluid, or solidified inflation fluid, within the balloon.Advantageously, this allows frozen inflation fluid to be thawed quicklyif required.

In order to support the sensors, means for heating and any other devicesat the distal end of the catheter, the system may further compriseconnectors to one or more power supplies, data interfaces, or othersignal processing units, configured to provide a power supply, controlsignals and to convert sensor signals into data. Electrical wires may behoused in the catheter shaft together with the lumens or along theoutside of the catheter shaft.

Preferably, the volume of the inflation fluid is fixed and small. Thisminimises the damage caused by any leakage. The injection of theinflation fluid to inflate the balloon may be automatically controlledand performed, for example, by an operator pressing a button.Alternatively, the inflation fluid may be injected manually.

According to known techniques, one or more portions of the catheter maybe radiopaque and/or include a radiopaque marker. This aids the operatorof the catheter.

The cooling elements are typically characterised by supply lumenprovided inside a return lumen. The supply lumen may be positionedcentrally within the return lumen but this is not essential. The supplylumen may alternatively lie along a side of the return lumen or be in noway fixed to the return lumen so that its position within the returnlumen can change.

Further embodiments of the invention include those in which the elongatecooling element is also the guide wire lumen. For example, the coolingelement itself may be configured to receive a guide wire such that aseparate guide wire lumen is not required. In embodiments wherein thecooling element comprises a return lumen provided inside a supply lumen,either the supply or the return lumen may be arranged to receive a guidewire. This provides the advantage of simplifying the design, therebyenabling the overall size of the shaft to be reduced, as well asoffering more structural support.

Further embodiments include a number of modifications and variationsthat can be made to the embodiments as described above. In particular,all of the dimensions provided in the figures are approximate andembodiments include catheter designs with different dimensions.Furthermore the dimensions may also vary depending on the size of thehuman or animal that is being treated. Throughout the present documentvarious features are described as lumens and tubes. These terms may beused interchangeably and said features may also be referred to asconduits.

In the above described embodiments the cooling element is preferablysubstantially straight and co-linear with the abutting end of the shaft.The cooling element may be rigid and non-flexible. However, the coolingelement is preferably flexible so that it can bend, as is appropriate ifthe balloon is positioned in a curved section of artery.

In the above-described operation of the system, operational temperaturesand pressures are provided. However, embodiments are in no way limitedto these operational temperatures and pressures. Moreover, theoperational temperatures and pressures may be varied depending on theapplication. In particular, embodiments include the catheter, and thesystem supporting the catheter, being operated according to thedisclosure in WO 2012/140439 A1, the entire contents of which areincorporated herein by reference.

The balloons according to embodiments may have a thinner membrane thanballoons used for angioplasty. However, embodiments also include usingballoons with the same thickness as those used in angioplasty so thatthe balloons advantageously act as a secondary barrier in case of a leakin the cooling tube.

Other embodiments of the invention will be apparent to those skilled inthe art from consideration of the specification and practice of theembodiments disclosed herein. It is intended that the specification andexamples be considered as exemplary only, with a true scope and spiritof the invention being indicated by the following claims.

1. A catheter comprising: a flexible heat transfer element provided onan outer surface of the catheter; a conduit arranged to supply aninflation fluid for inflating the flexible heat transfer element so asto form an inflated balloon; a guide wire lumen for receiving a guidewire; and an elongate cooling element arranged to cool said inflationfluid for inflating the balloon; wherein said cooling element and saidguide wire lumen are arranged inside the flexible heat transfer elementsuch that, when inflated the cooling element is substantially centralwithin the balloon and said guide wire lumen is parallel to and radiallyoffset from the cooling element; and wherein the guide wire lumen isprovided off-center with respect to the balloon.
 2. The catheteraccording to claim 1, wherein said cooling element is arranged withinthe balloon so that, in use, the inner surface of the balloon is cooledsubstantially uniformly by the cooling element around the circumferenceof the balloon.
 3. The catheter according to claim 1, wherein theelongate cooling element extends along a longitudinal axis in adirection parallel to a central axis of the balloon.
 4. The catheteraccording to claim 3, wherein an outside of the guide wire lumen isradially offset from the central axis of the balloon by at least 0.5 mm,preferably 0.5 mm to 1.8 mm.
 5. The catheter according to claim 1,wherein the cooling element is arranged inside the flexible heattransfer element such that, when viewed in the plane normal to thelongitudinal axis of the cooling element, the cooling element isprovided substantially within the center of the balloon.
 6. The catheteraccording to claim 1, wherein the flexible heat transfer element isconfigured to inflate into a substantially cylindrical balloon havingfirst and second asymmetric ends.
 7. The catheter according to claim 6,wherein the conduit arranged to supply an inflation fluid, the guidewire lumen and the elongate cooling element are provided inside a shaft,wherein the flexible heat transfer element is adhered to the shaft atthe first end, and wherein the flexible heat transfer element is adheredto the guide wire lumen at the second end.
 8. The catheter according toclaim 1, wherein said cooling element comprises a first tube providedinside a second tube, wherein the first tube is substantially parallelto the second tube; and the second tube is configured to receive a flowof a coolant for cooling the cooling element from the first tube.
 9. Thecatheter according to claim 1, wherein, in use, the first tube and thesecond tube are operated such that the pressure of the second tube islower than the first tube.
 10. The catheter according to claim 1,wherein said cooling element comprises an elongate cooling chamberconfigured to receive coolant from the first tube and provide saidcoolant to the second tube.
 11. The catheter according to claim 10,wherein the elongate cooling chamber is arranged co-linearly with an endof the second tube, wherein said cooling element further comprises arestriction tube configured to convey the coolant from the first tube tothe cooling chamber, wherein said restriction tube has narrower internaldiameter than the first tube, and wherein the restriction tube andcooling chamber are configured such that when the coolant conveyed alongthe first tube as a liquid, at least some of the coolant undergoes aphase change in the restriction tube and/or in the cooling chamber andreturns through the second tube as a gas.
 12. The catheter according toclaim 1, wherein said balloon is substantially cylindrical.
 13. Thecatheter according to claim 1 wherein, in use in a vessel, the inflatedflexible heat transfer element occludes fluid flow between the walls ofthe vessel and the inflated flexible heat transfer element.
 14. Thecatheter according to claim 1, wherein the conduit is further configuredto provide a return flow of the inflation fluid of the flexible heattransfer element.
 15. The catheter according to claim 1, wherein thecentral axis of the balloon extends through the elongate coolingelement, in the direction of the longitudinal axis of the coolingelement.
 16. The catheter according to claim 1, wherein said coolingelement is not attached to the end of the guide wire lumen and whereinsaid cooling element is configured such that, when in use, the flow ofthe coolant causes the cooling element to vibrate.
 17. The catheteraccording to claim 1, wherein the flexible heat transfer element hassingle walled outer membrane.
 18. The catheter according to claim 1,further comprising a heater for heating the inflation fluid, orsolidified inflation fluid, of the flexible heat transfer element. 19.The catheter according to claim 1, wherein the conduit, the guide wirelumen and the cooling element protrude from a shaft, and wherein, insidethe shaft, the cooling element has an outer surface having aflattened-circular shape when viewed in the plane normal to thelongitudinal axis of the cooling element.
 20. The catheter according toclaim 1, wherein the conduit, the guide wire lumen and the coolingelement protrude from a shaft, the shaft comprising a solid bodyoccupying the regions between the conduit, the guide wire lumen and thecooling element.